TAO-kinase 3 governs the terminal differentiation of NOTCH2-dependent splenic conventional dendritic cells
| Autor: | Sofie Van Gassen, Bart N. Lambrecht, Bastiaan Maes, Kim Deswarte, Lana Vandersarren, Connie M. Arthur, Manon Vanheerswynghels, Sean R. Stowell, Matthias Vanderkerken, Margaret E. Kirkling, Wendy Toussaint, Boris Reizis, Daniel H. Conrad, Philippe Pouliot, Hamida Hammad, Liesbet Martens |
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| Přispěvatelé: | Pulmonary Medicine |
| Rok vydání: | 2020 |
| Předmět: |
CD4-Positive T-Lymphocytes
Notch signaling pathway Spleen Biology 03 medical and health sciences 0302 clinical medicine Immune system Protein Domains Antigens CD Intestine Small medicine Animals Receptor Notch2 Transcription factor 030304 developmental biology 0303 health sciences Multidisciplinary Kinase Cell Differentiation Dendritic Cells Dendritic cell Biological Sciences In vitro Cell biology Mice Inbred C57BL Phenotype Lymphatic system medicine.anatomical_structure Gene Expression Regulation Protein Kinases Signal Transduction 030215 immunology |
| Zdroj: | Proceedings of the National Academy of Sciences Proc Natl Acad Sci U S A Proceedings of the National Academy of Sciences of the United States of America, 117(49), 31331-31342. National Academy of Sciences |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.2009847117 |
| Popis: | Antigen-presenting conventional dendritic cells (cDCs) are broadly divided into type 1 and type 2 subsets that further adapt their phenotype and function to perform specialized tasks in the immune system. The precise signals controlling tissue-specific adaptation and differentiation of cDCs are currently poorly understood. We found that mice deficient in the Ste20 kinase Thousand and One Kinase 3 (TAOK3) lacked terminally differentiated ESAM(+) CD4(+) cDC2s in the spleen and failed to prime CD4(+) T cells in response to allogeneic red-blood-cell transfusion. These NOTCH2- and ADAM10-dependent cDC2s were absent selectively in the spleen, but not in the intestine of Taok3(−/−) and CD11c-cre Taok3(fl/fl) mice. The loss of splenic ESAM(+) cDC2s was cell-intrinsic and could be rescued by conditional overexpression of the constitutively active NOTCH intracellular domain in CD11c-expressing cells. Therefore, TAOK3 controls the terminal differentiation of NOTCH2-dependent splenic cDC2s. |
| Databáze: | OpenAIRE |
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